Diabetes reduces autophosphorylation of retinal insulin receptor and increases protein-tyrosine phosphatase-1B

Raju V S Rajala1, Brandt Wiskur, Masaki Tanito

  • 1Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. raju-rajala@ouhsc.edu

Abstract

Insights

Diabetes reduces retinal insulin receptor (IR) autophosphorylation by increasing protein-tyrosine phosphatase-1B (PTP1B) activity. PTP1B regulates IR phosphorylation in the retina.

Area of Science:

  • Ophthalmology
  • Endocrinology
  • Molecular Biology

Background:

  • Protein-tyrosine phosphatase-1B (PTP1B) is known to negatively regulate insulin signaling.
  • The role and expression of PTP1B in the retina remain largely uncharacterized.
  • Understanding PTP1B's function in the retina is crucial for comprehending diabetic retinopathy.

Purpose of the Study:

  • To investigate the expression, activity, and functional role of PTP1B in the retina.
  • To examine the relationship between the retinal insulin receptor (IR) and PTP1B in normal and diabetic mouse models.
  • To determine how diabetes affects PTP1B and IR interaction and phosphorylation in the retina.

Main Methods:

  • Immunohistochemistry was used to localize IR and PTP1B expression in retinal tissues.
  • IR activation was assessed via antibodies targeting phosphotyrosine.
  • PTP1B activity was measured in immunoprecipitates, and its interaction with IR was studied using glutathione-S-transferase fusion proteins.

Main Results:

  • PTP1B is expressed in nonphotoreceptor layers and rod photoreceptor inner segments; IR is predominantly in rod inner segments.
  • Diabetic mouse retinas showed reduced IR autophosphorylation and increased PTP1B activity.
  • In vitro studies confirmed PTP1B dephosphorylates and interacts with the autophosphorylated IR.

Conclusions:

  • Diabetes mellitus leads to decreased retinal IR autophosphorylation and elevated PTP1B activity.
  • PTP1B plays a significant role in regulating the phosphorylation status of the retinal IR.
  • These findings highlight PTP1B as a potential therapeutic target for diabetic eye complications.

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